P1229: RITUXIMAB-DOSE-ADJUSTED EPOCH (R-DA-EPOCH) IN PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA (PMLBCL): REAL-LIFE EXPERIENCE ON 225 PATIENTS FROM 4 COUNTRIES
Authors: T. Vassilakopoulos, B. Ferhanoglu, N. A. Horowitz, J. Apostolidis, Z. Mellios, L. Kaynar, M. Zektser, A. Symeonidis, A. Piperidou, C. Kalpadaki, O. M. Akay, S. C. Atalar, A. Sayyed, E. Katodritou, T. Leonidopoulou, S. Papageorgiou, T. Tadmor, O. Gutwein, S. Karakatsanis, C. Ganzel, G. Karianakis, G. Isenberg, G. Gainaru, E. Vrakidou, M. Palassopoulou, M. Ozgur, M. Siakantaris, S. Paydas, P. Tsirigotis, M. Tsirogianni, E. Hatzimichael, T. F. Tuglular, C. Chatzidimitriou, A. Liaskas, M. A. Lefaki, N. Kanellias, P. Zikos, A. Koumarianou, A. Gafter-Gvili, M. Angelopoulou, T. Karmiris, R. Gurion
Journal: HemaSphere (2022)

Background: Real-life studies of moderate size have shown satisfactory but less impressive results compared with the initial study of R-da-EPOCH in PMLBCL. However, the strategies regarding the use of consolidative radiotherapy (RT) and the compliance with the strict instructions on dose escalation have not been studied. Aims: To assess the clinical outcomes and prognostic factors after R-da-EPOCH, the use of consolidative RT and protocol compliance in a multinational real-life setting. Methods: 225 patients (≤60 years) were enrolled from 18 Greek (n=114), 6 Israeli (n=57), 6 Turkish (n=34) and a single Saudi Arabia center (n=20). Consolidative RT was given at the treating physician’s discretion and was highly affected by PET/CT results. Results: The median age of the patients was 33 years (16-60), 139 (62%) were females, 40% had B-symptoms, 32% extranodal involvement (E or stage IV), 18% PS≥2, 84% elevated LDH (35% highly elevated≥2xnormal). The median follow-up was 32.5 months (2-97). Among 200 evaluable patients with conventional response, who would be potentially eligible for RT, RT was spared in 169 (84%); 31 received RT mainly for Deauville 4 (or rarely Deauville 5) residuals. The 5-year Freedom From Progression (FFP) was 86%. However, 4 patients developed therapy-related (t-) AML at 10.5-22 months from treatment initiation, while in 1st remission, and one Hodgkin lymphoma, for a 2-year event-free survival of 83%, if considered as events. The 5-year overall survival (OS) was 92% with 14 disease-related deaths (1 toxic). Protocol violations were common (52%), mainly consisting of insufficient dose escalation despite the absence of prohibitive toxicity. Among 209 patients with available data, 58% reached level ≥3 and 29% ≥4 (73% and 46% among those with strict protocol adherence). The 5-year FFP was 89% vs 84% for patients with strict protocol adherence or not (p=0.37); OS was not also different. FFP did not differ according to the final level reached (≥3 or ≥4; both p>0.20). A more detailed analysis of outcome according to the degree of protocol violations is currently ongoing. The prognostic systems including any extranodal involvement (E/IV) and highly elevated LDH (≥2x) or bulk marginally or significantly affected prognosis: Considering the E/IV-LDH model, the 5-year FFP was 89%, 84% and 73% for patients with 0, 1 or 2 adverse factors (p=0.14), while 5-year OS was 97%, 91% and 81% (p=0.08). The corresponding figures for the E/IV-bulk model were 90%, 89% and 75% (p=0.026) for FFP and 98%, 94% and 83% for OS (p=0.01). Thus, patients with both risk factors had 5-year FFP rates 73-75% and 5-year OS 81-83%. Summary/Conclusion: In the largest series reported so far for R-da-EPOCH in PMLBCL, FFP appeared somewhat but not impressively better than the expected with R-CHOP. However, consolidative RT was safely omitted in ~85% of responders mainly based on PET findings. OS was 92%. However, the appearance of 4 cases of t-AML among 225 patients is worrisome. Significant dose-escalation violations were recorded in the real-life; their impact on outcomes appears to be modest and is further evaluated in detail while the series is also expanded with inclusion of even more patients. Patients with multiple adverse factors appear to do better than with R-CHOP, while those with 0-1 factor have similar outcomes to R-CHOP but with minimal consolidative RT.